The importance of the endogenous cannabinoid system in various neuropsychiatric disorders

Abstract

The endogenous cannabinoid system was first described in 1988. There are two specific receptors, the CB2-receptor, located in the lymphatic system (spleen, lymphocytes), and the CB1-receptor occurring predominantly in the central nervous system. The CB1-receptor shows a distinct distribution in the CNS with a very high density in the cerebellum, the basal ganglia and in the hippocampus. In 1992 endogenous ligands of the cannabinoid system were discovered for the first time (e.g. anandamide and 2-arachidonylglycerol). The physiological role of these arachidonic acid derivates is still unclear. Implications of these recent discoveries for the Gilles de la Tourette syndrome, ischaemic brain lesions, schizophrenic psychoses and opiate drug dependence are described. A dysregulation in the endogenous cannabinoid/anandamide system could possibly play an import role in the etiology of Gilles de la Tourette syndrome and schizophrenic psychoses; administration of cannabinoids affects the symptoms of the Gilles de la Tourette syndrome positively, whereas cannabinoids probably have rather negative effects in schizophrenic psychoses. In ischaemic brain lesions cannabinoids seem to have a neuroprotective effect; they appear to minimize the extent of a lesion by reduction of glutamate release. Additionally the meaning of the endogenous cannabinoid system for the development of opioid drug dependency is discussed and interactions between the endogenous opioid system and the endogenous cannabainoid system are pointed out. This is of interest since it could be shown in animal experiments that the absence of CB1 receptors reduces the positive reinforcement of opiate administration.